The blood pressure of one-kidney hypertensive rabbits can be lowered to normal by direct immunization with extracts of hog kidney cortex. Our evidence indicates that an unknown antigenic factor (antigen M) is responsible for the development of a cross-reacting antibody that neutralizes a substance essential for the maintenace of elevated blood pressure in the animal model. A number of active preprations of antigen M have been made from both whole hog kidney and hog kidney cortex by extracting in the presence of a "cocktail" of proteolytic enzyme inhibitors. Our most active preparations are obtained from hog kidney cortex by treatment at pH 1.6 and 0 degrees, fractionation with ammonium sulfate between the limits of 0.75 and 2.75 M, and chromatography on a pepstatin affinity column. The latter step is particularly useful for the purpose of purification and eliminating substances which may interfere with the immunological response during assay. Active fractions with isoelectric points of 3.1 and 3.5 have been obtained by preparative isoelectric focusing. We are also attempting to identify antigen M by careful comparison of crossed immunoelectrophoretic plates of active and inactive preparations. Similar efforts are underway using vertical slab gel polyacrylamide elecrophoresis of 125I labeled antigen isolated from the antigen-antibody complex with protein A.